Available online 30 April 2024, 100873

Author links open overlay panel, , , , , ABSTRACTIntroduction

Resistance to chemoradiation therapy results in poor prognosis and relapse in a sizeable percentage of cervical cancer patients. Toxicities and long-term side effects associated with radiation also warrant the need for molecules that could sensitize cells to radiation therapy. Naturally-derived compounds are a reservoir of non-toxic, potentially effective radiosensitizers of therapy-resistant tumors. This study evaluates the anti-tumorigenic properties of Aloe vera extracts.

Methods

Phenotypic assays and biochemical experiments like flow cytometry, real-time quantitative PCR, immunofluorescent imaging, western blotting, migration, and wound healing assays were used to determine the effect of Aloe vera on cervical cancer cell lines.

Results

While Aloe vera treatment caused no significant changes to proliferation, survival, and cell cycling profiles, the expression of periostin (POSTN), a molecule known for its association with stem-like cancer cells, decreased significantly. Phenotypically, Aloe vera treatment led to diminished clonogenicity and migratory abilities. Finally, combinatorial treatment of cells with Aloe vera and atorvastatin (a pan Rho GTPase inhibitor) before radiation therapy resulted in a marked decrease in cell survival.

Conclusion

Our findings prove that Aloe vera treatment leads to reduced expression of POSTN, and adversely affects self-renewal and migration. Importantly, this work provides evidence that Aloe vera, in combination with atorvastatin, could serve as potential radiosensitizers of cancer cells.

Section snippetsINTRODUCTION

According to the WHO, cervical cancer ranks fourth amongst the most common cancers in women. Cancer of the cervix is emerging as a significant health concern, particularly in economically challenged regions, with 90% of the new cases and deaths recorded in 2020 occurring in low- and middle-income countries. Importantly, cervical carcinomas identified at early stages (localized SEER stage) have a high 5-year survival rate (92%), whereas 5-year survival rates of those identified at the distant

Cells lines and culturing conditions

Squamous cervical carcinoma-derived cell lines, SiHa and CaSki, were used in this study. While SiHa cells originate from primary tumors, CaSki cells were isolated from secondary tumor outgrowths. Cells were cultured in Dulbecco’s Modified Eagle Medium (DMEM) (Invitrogen Catalogue number: 12100046), supplemented with 10% FBS (Foetal Bovine Serum) (HiMedia Catalogue number: RM10409) and penicillin-streptomycin (Invitrogen Catalogue number:15140148) at 37°C and 5% CO2. The cultures were tested for

Effect of Aloe vera on cell survival and cell cycling profiles

SiHa cells treated with different volumes of the Aloe vera extract (AV) were assayed for changes in cell survival. The WST assay revealed no significant difference in cell survival at the end of 24h (a=25µl, b=50µl, and c=100µl per ml of media) (Figure 1A-i). However, increasing volumes of the extract led to decreased cell survival. Since cells treated with the respective vehicle controls (EtOH) had similar levels of cytotoxicity, the observed decrease in cell survival with the increase in

DISCUSSION

Concurrent chemoradiation therapy (CRT) is the gold standard of treatment for locally advanced carcinoma of the cervix (Morris et al., 1999, Rose et al., 1999, Whitney et al., 1999). However, radiation in combination with cisplatin results in only a marginal increase in survival, with an improvement of around 10% in 5-year survival rates, in comparison with radiotherapy alone (Bernier et al., 2004). It therefore becomes necessary to identify radiosensitizers that can facilitate increased cell

Funding Statement

We would like to thank the Science and Engineering Research Board (SERB), India for funding via the grant awarded to Dr. Sweta Srivastava [ECR/2016/000812]. Pavana Thomas has been awarded a fellowship by the Council for Scientific and Industrial Research (CSIR), India for the course of her Ph.D.

Uncited reference

(Yu et al., 2018)

Ethical Statement

We ensure that all research is conducted in accordance with ethical principles. No human subjects/samples from human subjects/animals were used in this study.

CRediT authorship contribution statement

Avinash H Udayashankara: Supervision, Writing – review & editing. Sweta Srivastava: Conceptualization, Formal analysis, Funding acquisition, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing. Deepika L Hiremath: Data curation, Investigation, Methodology, Validation. Swagatika Sahoo: Data curation, Investigation, Validation, Methodology. Sawani Mahajan: Data curation, Investigation, Validation. Pavana Thomas: Data curation, Formal analysis,

Declaration of Competing Interest

None

Acknowledgements

We would like to thank the Science and Engineering Research Board (SERB), India for funding via the grant awarded to Dr. Sweta Srivastava [ECR/2016/000812]. Pavana Thomas has been awarded a fellowship by the Council for Scientific and Industrial Research (CSIR), India for the course of her Ph.D.

COMPETING INTERESTS

The authors have no relevant financial or non-financial interests to disclose.

DISCLOSURE

The author reports no conflicts of interest in this work.

DATA AVAIL-ABILITY

Data sharing not applicable to this article as no datasets were

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