Shikonin Applications in Cancer Therapy

Shikonin is a naturally occurring naphthoquinone pigment extracted from the roots of Lithospermum erythrorhizon and related Boraginaceae species. It has attracted considerable attention for its broad-spectrum anticancer activity, manifesting through multiple mechanisms including induction of apoptosis, necroptosis and autophagy. Central to its efficacy is the generation of reactive oxygen species (ROS), which precipitate mitochondrial membrane depolarisation and endoplasmic reticulum (ER) stress, thereby activating both caspase-dependent and caspase-independent cell death pathways. Shikonin also modulates key signalling axes — for example, p38 MAPK, JNK and c-MYC — and can overcome chemoresistance by sensitising tumour cells to conventional agents. Preclinical studies have demonstrated its efficacy in leukaemia, melanoma, colorectal, gastric and lung cancer models, often with minimal toxicity to normal tissues. These multifaceted actions and its potential for synergistic combinations position Shikonin as a promising candidate for next-generation cancer therapeutics.

Research from Nature Portfolio

Recent studies have demonstrated that Shikonin effectively suppresses gastric cancer progression by inducing substantial ROS production, disrupting the mitochondrial membrane potential and triggering both caspase-dependent release of cytochrome C and caspase-independent nuclear translocation of apoptosis-inducing factor. In vitro and in vivo experiments further revealed that Shikonin enhances the sensitivity of gastric carcinoma cells to 5-fluorouracil and oxaliplatin, reducing tumour burden more effectively than standard chemotherapy alone and suggesting its value as a chemosensitising adjuvant to overcome drug resistance.

Shikonin Applications in Cancer Therapy publication trend

The graph below shows the total number of articles in shikonin applications in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Electrically charged oxygen derivatives that, in excess, induce oxidative damage and trigger programmed cell death pathways.

Mitochondrial membrane potential (MMP): The voltage gradient across the inner mitochondrial membrane essential for ATP synthesis; its loss signals mitochondrial dysfunction leading to apoptosis.

Endoplasmic reticulum (ER) stress: A condition arising from accumulation of misfolded proteins in the ER lumen, activating unfolded protein responses that can culminate in apoptosis or autophagy.

Chemo-sensitisation: The process by which agents enhance the susceptibility of cancer cells to cytotoxic effects of chemotherapy.

References

1. Shikonin Induces ROS-Dependent Apoptosis Via Mitochondria Depolarization and ER Stress in Adult T Cell Leukemia/Lymphoma. Antioxidants (2023).
2. Global Identification of Anti-Melanoma Cellular Targets by Photochemically Induced Coupling of L-Shikonin Reactions on the Surface of Magnetic Particles. Pharmaceutics (2024).
3. Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways. Artificial Cells Nanomedicine and Biotechnology (2019).
4. Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells. Oncotarget (2015).
5. Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species. Scientific Reports (2016).