‘Some Haakh Varieties Have High Anticancer Potential against Prostate and Lung Cancer Cells’

   

A junior scientist at SKUAST-K, Dr Khalid Zaffar Masoodi is an award-winning biotechnologist who has been working on cancer biology. Founder of Kashmir’s first faculty-led biotech company of Kashmir, Cashmir Biotech Pvt. Ltd, he has been working on low-cost, healthy, non-toxic, and safe designer foods to cure and prevent various disorders including cancer through futuristic functional foods. Currently, his laboratory’s research is related to the identification of anticancer molecules for prostate cancer from medicinal plants endemic to Kashmir. In a freewheeling interview with Masood Hussain, he offers his knowledge about awareness to deliver and contribute new innovations in biotechnology and research on the causes, treatment and prevention of cancer through anticancer functional foods, designer foods, and superfoods.

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KASHMIR LIFE (KL): The conventional wisdom is that local issues have local solutions. Can we have local solutions to local health issues as well?

Khalid Z Masoodi (KZM): There are more than 200 types of cancer throughout the world and we can classify cancers according to where they start in the body, such as breast cancer ovarian cancer, prostate cancer, lung cancer etc. We can also group cancer according to the type of cell they start in and these cancers are increasing day by day worldwide. 20 per cent of these cancers are genetic in origin according to studies and 80 per cent are caused by environmental factors, food habits and lifestyle changes. These factors mutate the DNA and cause changes in normal cell growth.

For example, our bodies intake 210 mcg per day of cancer-causing hormone-disrupting chemical phthalates found in every soft and flexible plastic we use in our daily life. The beverages in the plastic bottle are injurious as these plastic containers have phthalates that bind to endocrine receptors and overexcite them resulting in malignancies.

In dark chocolates toxic metals are lurking, it is a state of serious concern as they cause cancer. Preservatives used in foods contain carcinogenic components. Every single person consumes 150 pounds or 60-88 kg of preservatives in a year. Most of the preservatives’ in vogue contain acrylamide which is carcinogenic. The most popular fast food of today’s generation is French fries, potato chips, pizza, and cold drinks in which the presence of Acrylamide and glycidamide has been found. Burgers contain Heterocyclic aromatic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Studies show HCAs and PAHs cause changes in DNA that may increase the risk of cancer. Pizza preservatives – TBHQ and BHA, has been identified as human carcinogen. 1n 2016 as we all know potassium bromate used to soften bread and in many other food items was banned in India as they were found carcinogenic during the course of research.

The estimated numbers of cancer in 2022 were 17 per cent in the case of breast cancer, 14 per cent in prostate cancer, 4.9 per cent in thyroid cancer, and lung cancer was estimated to be 14.3 per cent worldwide. Prostate cancer is the second leading cause of cancer-related deaths and the primary diagnosed cancer in men. No defined therapy against prostate cancer is present. Drugs cease to function after treatment in most cases. There is a need to cure and prevent deadly diseases with a healthier approach.

We define here the concept of Designer Foods that have added health benefits. Designer foods are normal foods fortified with health-promoting ingredients. These foods are similar in appearance to normal foods and are consumed regularly as a part of the diet. These foods are safe, non-toxic, organic, are cost-effective while the drugs available are cost-extensive and unaffordable by the majority classes of society and have added off-target effects.

We believe that a smart diet containing anticancer small molecules and molecules that can treat these disorders can help prevent these disorders The changing food habits of the modern world have changed, from green food (green vegetables), and herbs, to fast food, which is the main concern. We have experimentally shown that these greens, underutilised plants have high antioxidant properties. Some of our studies found some Haakh varieties have high anticancer potential against prostate and lung cancer cells.

KL: Can you tell us about your academic journey?

KZM: I completed my schooling at Burn Hall School, Srinagar and continued further studies at AMU. I completed my BSC (Hons) in Botany from AMU and pursued MSc and PhD in Plant Biotechnology from Jammu University under the mentorship of Prof Manoj K Dhar, former VC, University of Jammu, which I completed in 2010.

KL: What were the takeaways from your PhD?

KZM: During my PhD, I worked on the reconstruction of carotenoid biosynthetic pathway genes from purple-black carrot (Daucuscarota L). We successfully engineered E Coli that produced Lycopene and beta-carotene. Besides, we increased the production of these carotenoids using the Amplification Promoting Sequence, which increased the copy number of genes and hence their transcription and translation. We also worked on anthocyanins that act as effective natural food bio-colourant and real-time indicators of food spoilage that later helped in developing a smart gel that changes colour with a change in pH and can be used in food industries, biomedical industries and agriculture industries. Synthetic food colours pose a greater threat to humans and are responsible for causing various types of cancers and cardiovascular diseases.

KL: You continued your post-doctorate in the same field or we changed the subject?

KZM: The main expertise in cancer biology was gained during my post-doctoral associateship at the University of Pittsburgh, Pennsylvania, USA. There, I simultaneously worked on many projects related to gene and drug discoveries against prostate cancer.

We found the role of many genes in prostate cancer progression like ELL2, DHX15, PABPCA, EAF2, PRP8 etc. I also helped discover new androgen receptors targeting small molecules. I also increased the efficacy of IADT, the study which came out in the Journal of Urology, Journal of Endocrinology, Oncogene, Molecular Cancer Therapeutics, and PLoS One.

After my return from the USA, I worked as a Senior Resident at SKIMS, Soura for a short time before joining the Division of Plant Biotechnology, SKUAST-Kashmir as an Assistant Professor. The takeaway for me was that cancer cells are smart and if you try to target them through inhibition of the AR pathway they will salvage their survival through the PI3Kinase pathway. In metropolitan India, prostrate is now the third diagnosed cancer.

KL: You worked on cancer and then joined SKUAST-K which is all about agriculture. Is not it an interesting twist in the story?

KZM: It is always a challenge but biotechnologists revolve around the central dogma of molecular biology so DNA, RNA and proteins are the same which makes every organism. Upon my joining SKUAST-K, I surveyed various regions of Jammu and Kashmir to utilize the rich flora for new therapeutics against cancer.

It is very important that we do translational research that can result in an end product that can be commercialized and can be more useful than a mere publication or a patent. We knew that 60 per cent of the drugs in the market are plant-based or their analogues.

A rich repertoire of around 3054 medicinal and aromatic plant species (MAPs) are endogenous to Kashmir but were not explored for anticancer properties against prostate cancer through transcriptomics and AR targeted approach earlier. In a drug discovery programme initiated at SKUAST-K funded SERB, we screened 25,000 medicinal plant extracts from Kashmir’s around 350-400 medicinal plants. It resulted in the discovery of 16 new anticancer molecules against prostate cancer. Of these 16 molecules, five were from edible underutilised plants. Our laboratory has filed eight patents in the last three years.

Dr Khalid Zaffar Masoodi (SKUAST)

KL: Is there something that you can share with us about the new molecules you discovered?

KZM: The molecule SKIDDDL-1 present in the TaxO was the best among all the edible plants, which has been consumed for ages in Kashmir as a food supplement and as a vegetable. Over time, however, its use has diminished. This molecule effectively targeted androgen receptors in prostate cancer and decreased cellular progression, cancer cell migration (metastasis) in vitro and reduced tumour volume, and doubled the life expectancy in the mice xenograft model. A smart diet may help reduce the risk of developing prostate cancer, slow the progression of the disease, and prevent invasiveness and metastasis.

Awaiting a patent, we designed Magic Foods – a range of safe, non-toxic, plant-based anti-prostate cancer futuristic functional foods fortified with our secret TaxO that can be consumed on daily basis by populations worldwide that are at high risk of getting this peculiar cancer. The technology is cheap, safe and has no side effects.

Since SKUAST-K is the first Farm University to implement NEP 2020, now the faculty is permitted to have a start-up. I was joined by my two MSc students as directors of the faculty-led start-up. They are still studying but are job providers at the same time.

When we were doing this research, we had a great visitor from the University of  Buffalo, Prof Samina Raja. We thought we can give something better to humanity if we worked together. So we have one collaborative project Haakh.

I am glad to share that soon you will have an anticancer Haakh variety. We are in the final stages of assessment and experimentation and after a thorough study of about 70 different variants of haakh we found some variants that have good activity against lung and prostate cancer.

The American University provided us with a small grant which we utilised in DNA bar-coding our Haakh, which can be accessed through GenBank. SERB, DST, Government of India has been kind enough and given me three successive grants without which what we did would not have been possible. My NC has always been my great support.

KL: Kashmir is India’s main apple basket. Have you worked on apple scab?

KZM: For Kashmir, agriculture is the backbone, especially the apple. The scab results in almost 30-40 per cent loss in apple. To prevent it we use around Rs 325 crore worth of fungicides which eventually go into our bodies through water and food. That is why people living around apple orchards have a higher incidence of endocrine-related issues.

We have worked on biotechnological approaches to scab pathogens in which we have identified new genes that can be used for producing cisgenic apples for scab resistance. This study was also published in one of the reputed high-impact journals. We used comparative transcriptome technology (RNA-Seq) for research that showed some genes expressed in the Maharaji apple and wild-type genotypes like Florina are not expressed in red delicious, so these genes can be transferred into red delicious to make the variety scab resistant. The process of producing cisgenic apples and breeding both techniques is underway.

KL: You have also identified some new wilt-causing pathogens. Tell us something about this.

KZM: One of my PhD scholars, Dr Tasmeen Parihar has identified six new Fusarium spp infecting solanaceous crops that were not earlier known to cause wilt in chilli, brinjal, tomato and capsicum. These findings came out recently in reputed journals.

We have many scientists in collaboration within and outside institutes. I am lucky to have good collaborations with Dr Zahoor A Bhat (Plant Pathology), Dr Khalid Bhat (Fruit Science), Dr Khursheed (Vegetable Sciences), Prof Mudasir Andrabi (Animal Biotechnology), Dr Tawheed Amin (FST) and many more.

KL: There is a major ethical debate regarding biotechnology, especially GM foods.

KZM: In biotechnology, we always have to face challenges related to transgenic plants but the fact is that in the near future (2050) breeding techniques will not be able to fulfil the need of the growing population. We will have to move towards biotechnology to feed the growing population of around 10 billion.

CRISP-Cas technology will enable us to knock out the antibiotic genes used in transgenic progress and we will have transgenic plants with only the gene of interest and not these antibiotic-resistant genes. Besides, we also use recombinant-based excision repair to make Cisgenic Apple. Since this research is going on we will have soon some good results.

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