Current Science

Ashutosh Chauhan ¹, Rani Ojha ¹, Deepak Kumar Semwal ², Satyendra Prasad Mishra ³, Ruchi Badoni Semwal ⁴

Affiliations
1 Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, IN
2 Department of Phytochemistry, Uttarakhand Ayurved University, Harrawala, Dehradun 248 001, IN
3 Uttarakhand Ayurved University, Harrawala, Dehradun 248 001, IN
4 Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, ZA

Abstract

Renal cell carcinoma (RCC) develops resistance to most of the conventional therapies. In recent years inhibitors are being used to interfere with growth of cancer cells at molecular level and are found to be the most effective treatment option. However, some patients have to deal with severe side effects. Till date there have been no specific predictive biomarkers available to predict the target response and patient's stratification. We evaluate the expression of speckletype POZ protein (SPOP) as a predictive biomarker in the presence of mTOR target therapy. Tissue samples were collected after nephrectomies from patients with RCC. Further primary culture was established from tissues of low- and high-grade RCC. Working concentration of inhibitors (CCI-779 and SB203580) was selected by MTT assay on A-498 cell line. Western blot was performed to study the p38MAPK, mTOR and SPOP protein expression. Primary culture showed more than 70% positivity for pan-cytokeratin. The concentration of 20 μM of CCI-799 and 25 μM SB203580 caused 30% and 20% cell death respectively. Expression of SPOP protein was decreased in CCI-779-treated cells. The combined treatment of CCI-779 and SB203580 had more inhibitory effects on SPOP in all cells types. However, SB203580 had no effect on SPOP expression. The results underline that, SPOP could be used as a potential predictive biomarker to assess the response of therapy with mTOR inhibitor (CCI-779).

Keywords

Protein Expression, Predictive Biomarker, Renal Cell Carcinoma, Target Therapy.

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Deepak Kumar Semwal ¹, Ashutosh Chauhan ², Ruchi Badoni Semwal ³, Debabrata Sircar ⁴, Partha Roy ⁴, Jörg Lehmann ⁵

Affiliations
1 Department of Phytochemistry, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Harrawala, Dehradun 248 001, IN
2 Department of Biotechnology, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Harrawala, Dehradun 248 001, IN
3 Department of Chemistry, Pt Lalit Mohan Sharma Government Postgraduate College, Rishikesh 249 201, IN
4 Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, IN
5 Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, Perlickstr. 1, 04103 Leipzig, DE

Abstract

In the current scenario, developing treatments, identifying cures and formulating intervention strategies to fight against the COVID-19 outbreak, have become the major concern for researchers globally. Several studies have confirmed the molecular pathway of COVID-19 virulence that involves activation of proteins like angiotensin-converting enzyme 2 (ACE2), angiotensin (AT) receptor which is mainly AT1, and transmembrane protease serine 2 (TMPRSS2). Since the virus needs the involvement of these proteins, over and above its spike protein, for activation and infecting the host, it is obvious that targeting or blocking the activation of these molecules may play a critical role in the development of therapeutics for the cure and management of COVID-19. Many studies have been reported and several are ongoing to find a cure using these molecules as a target. While initially COVID-19 was thought to be affecting the human respiratory system, recent shreds of evidence indicate that this infection can reach beyond the lungs. It can invade and rampage almost all the organs in the body, and ‘cytokine storm’ is considered to be responsible for this. The reason for disease severity is not what matters anymore now, everyone is hoping for a cure soon enough. Therefore, there is an urgent need to search for some novel drugs/chemicals. Towards this end, natural products can contribute immensely since they have a long history of usage for the cure and management of various ailments, including viral infections. Various natural products (mainly from plants) have structural similarities to the molecules which by AT has been shown to interact with targets used by COVID-19 during its infection. This is indeed a positive indication for the development of natural products-based therapeutics. This aspect, therefore, warrants serious consideration for the cure and management of the COVID-19 pandemic.

Keywords

Coronavirus, Cure And Management, Herbal Medicine, Natural Products, Pandemic.

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