L-ascorbic acid Synergizes with Paclitaxel to Enhance Anti-cancer Efficacy in Skin Cancer Cells

Rajendra Marathe; Pawan Pawar; Bharti Rathod; Preeti Singh; Sudip Konar; Omkar Wakale; Debjani Dasgupta; Matthew D. Blunt; Arindam Banerjee

doi:10.31557/APJCB.2026.11.2.525-533

Authors

Rajendra Marathe LifeSenz Cancer Research Labs Private Ltd. Mumbai, India.
Pawan Pawar LifeSenz Cancer Research Labs Private Ltd. Mumbai, India.
Bharti Rathod LifeSenz Cancer Research Labs Private Ltd. Mumbai, India.
Preeti Singh LifeSenz Cancer Research Labs Private Ltd. Mumbai, India.
Sudip Konar LifeSenz Cancer Research Labs Private Ltd. Mumbai, India.
Omkar Wakale LifeSenz Cancer Research Labs Private Ltd. Mumbai, India.
Debjani Dasgupta School of Biotechnology and Bioinformatics, D.Y. Patil Deemed to be University, Navi Mumbai, India.
Matthew D. Blunt Faculty of Medicine, University of Southampton, United Kingdom. https://orcid.org/0000-0003-1099-3985
Arindam Banerjee LifeSenz Cancer Research Labs Private Ltd. Mumbai, India. https://orcid.org/0000-0002-9382-5874

DOI:

https://doi.org/10.31557/APJCB.2026.11.2.525-533

Keywords:

Skin cancers, melanoma, non-melanoma, LAA, paclitaxel, combination therapy, CD44, GLUT 1, PI3K

Abstract

Background: Skin cancers with two major subtypes, melanoma and non-melanoma cases are rising worldwide. Paclitaxel has been used as an advanced stage therapeutic option in skin cancers, however, therapy resistance and metastasis are a limitation to its efficacy. L-ascorbic acid on the other hand is less toxic and has been demonstrated to possess both anti-cancer and pro-immune activities in clinical and preclinical settings.

Methods: The A375, melanoma cell line and the A431, non-melanoma cell line were used to determine efficacy between single agent paclitaxel and combination with L-ascorbic acid by multiple cells based functional assays including cytotoxicity, invasiveness, cancer stem cell specific functions and molecular assessments by quantitative PCR. Low glucose conditions and/or adaptations were also used to determine the impact of differential glucose concentrations on drug combination efficacy.

Results: Functional and transcriptomics data demonstrated that compared to single agent paclitaxel, the combination of paclitaxel with L-ascorbic acid restricted A375 and A431 cell growth potential, cellular invasiveness and cancer stem cell like-cells. Low glucose conditions further enhanced the superiority of the combination therapy.

Conclusion: This study reveals that L-ascorbic acid may improve the current therapeutic limitations associated with paclitaxel in skin cancers. Importantly, this combination is equally effective in both melanoma and non-melanoma based in vitro cell model systems.