Preprint / Version 1

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Authors

  • Suneel Kumar Bio-Design Innovation Centre, Rani Durgavati University, Jabalpur 482 001, India
  • Sardul Sandhu Bio-Design Innovation Centre, Rani Durgavati University, Jabalpur 482 001, India
  • Kassidy Webber College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
  • Kwang-Seok Ahn Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
  • Gautam Sethi Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
  • Chakrabhavi Mohan Department of Studies in Molecular Biology, University of Mysore, Mysuru 570 006, India
  • Hardeep Tulli Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala 133 207, India
  • Ravindra Aharwal Department of Botany, Government College Kurai, Seoni 480 880, India
  • Stephen Mathew Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
  • Anupam Bishayee College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA

Keywords:

withaferin A, cancer, apoptosis, angiogenesis, chemoresistance, formulations

Abstract

Cancer represents the second most deadly disease and one of the most important public health concerns worldwide. Surgery, chemotherapy, radiation therapy, and immune therapy are the major types of treatment strategies that have been implemented in cancer treatment. Unfortunately, these treatment options suffer from major limitations, such as drug-resistance and adverse effects, which may eventually result in disease recurrence. Many phytochemicals have been investigated for their antitumor efficacy in preclinical models and clinical studies to discover newer therapeutic agents with fewer adverse effects. Withaferin A, a natural bioactive molecule isolated from the Indian medicinal plant Withania somnifera (L.) Dunal, has been reported to impart anticancer activities against various cancer cell lines and preclinical cancer models by modulating the expression and activity of different oncogenic proteins. In this article, we have comprehensively discussed the biosynthesis of withaferin A as well as its antineoplastic activities and mode-of-action in in vitro and in vivo settings. We have also reviewed the effect of withaferin A on the expression of miRNAs, its combinational effect with other cytotoxic agents, withaferin A-based formulations, safety and toxicity profiles, and its clinical potential. Keywords: withaferin A, cancer, apoptosis, angiogenesis, chemoresistance, formulations

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