Cancer Research and Treatment

Original Articles

Synergistic Effect of Ionizing Radiation and β-lapachone against RKO Human Colon Adenocarcinoma Cells: Eun Jung Kim, In-Mi Ji, Ki-Jung Ahn, Eun Kyung Choi, Heon-Jin Park, Byung Uk Lim, Chang W. Song, Heon Joo Park; Cancer Res Treat. 2005;37(3):183-190. Published online June 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.3.183

Purpose

To reveal the interaction between β-Lapachone (β-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined β-lap treatment and radiotherapy for cancer treatment.

Materials and Methods

The cytotoxicities of various treatments were determined in vitro using clonogenic and apoptotic cell death. The changes in cell cycle distribution were studied using flow cytometry and an in vitro kinase assay. The tumor growth was studied using RKO tumors grown s.c. in the hind leg BALB/c- nuslc nude mice.

Results

β-lap caused clonogenic cell death and rapid apoptosis in RKO cells in vitro, in a dose dependent manner. The repair of sublethal radiation damage was almost completely inhibited when cells were maintained in β-lap during the interval between the two-dose irradiation. Flow cytometry study demonstrated that β-lap induced apoptosis, independent of the cell cycle phase, and completely prohibited the induction of radiation-induced G2 arrest in irradiated cells. The prohibition of radiation-induced G2 arrest is unclear, but may be related to the profound suppression of the p53, p21 and cyclin B1-Cdc2 kinase activities observed in cells treated with β-lap. The combination of β-lap and radiation markedly enhanced the radiation-induced growth suppression of tumors.

Conclusion

β-lap is cytotoxic against RKO cells, both in vitro and in vivo, and also sensitized cells to ionizing radiation by inhibiting sublethal radiation damage repair. β-lap is potentially useful as a potent anti-cancer chemotherapy drug and potent radiosensitizer against caner cells.

Citations

Citations to this article as recorded by

Chlorogenic Acid Enhances Beta‐Lapachone‐Induced Cell Death by Suppressing Autophagy in NQO1‐Positive Cancer Cells
Sahib Zada, Md Entaz Bahar, Wanil Kim, Deok Ryong Kim
Cell Biology International.2025; 49(5): 555. CrossRef
Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control
Fatemeh Shiridokht, Parniya Kehtari, Morteza Eskandani, Alireza Farajollahi, Somayeh Vandghanooni
International Journal of Pharmaceutics: X.2025; 10: 100419. CrossRef
Artemisia annua L. Polyphenols Enhance the Anticancer Effect of β-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells
Eun Joo Jung, Hye Jung Kim, Sung Chul Shin, Gon Sup Kim, Jin-Myung Jung, Soon Chan Hong, Choong Won Kim, Won Sup Lee
International Journal of Molecular Sciences.2023; 24(24): 17505. CrossRef
Radiotherapy-induced metabolic hallmarks in the tumor microenvironment
Anjali Mittal, Minal Nenwani, Itisam Sarangi, Abhinav Achreja, Theodore S. Lawrence, Deepak Nagrath
Trends in Cancer.2022; 8(10): 855. CrossRef
Natural products as chemo-radiation therapy sensitizers in cancers
Sabah Nisar, Tariq Masoodi, Kirti S. Prabhu, Shilpa Kuttikrishnan, Lubna Zarif, Summaiya Khatoon, Shahid Ali, Shahab Uddin, Ammira Al-Shabeeb Akil, Mayank Singh, Muzafar A. Macha, Ajaz A. Bhat
Biomedicine & Pharmacotherapy.2022; 154: 113610. CrossRef
Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis
Yang Zhou, Hui Yan, Qiang Zhou, Ruiling Feng, Penggao Wang, Fang Yang, Yaodong Zhang, Ziqiao Yuan, Bo Zhai
Frontiers in Pharmacology.2021;[Epub] CrossRef
Napabucasin (BBI 608), a potent chemoradiosensitizer in rectal cancer
Ganji Purnachandra Nagaraju, Batoul Farran, Matthew Farren, Gayathri Chalikonda, Christina Wu, Gregory B. Lesinski, Bassel F. El‐Rayes
Cancer.2020; 126(14): 3360. CrossRef
Using a novel NQO1 bioactivatable drug, beta‐lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer
Muhammad Shaalan Beg, Xiumei Huang, Molly A. Silvers, David E. Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J. Deberardinis, Matthew E. Merritt, Xian‐Jin Xie, Richard Leff, Daniel Laheru, David A. Boothman
Journal of Surgical Oncology.2017; 116(1): 83. CrossRef
2-[(4-Chlorophenyl)selanyl]-3,4-dihydro-2H-benzo[h]chromene-5,6-dione: crystal structure and Hirshfeld analysis
Julio Zukerman-Schpector, Karinne E. Prado, Luccas L. Name, Rodrigo Cella, Mukesh M. Jotani, Edward R. T. Tiekink
Acta Crystallographica Section E Crystallographic Communications.2017; 73(6): 918. CrossRef
β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells
E J Park, K-j Min, T-J Lee, Y H Yoo, Y-S Kim, T K Kwon
Cell Death & Disease.2014; 5(5): e1230. CrossRef
Enhancement of radiation effect using beta-lapachone and underlying mechanism
Ki Jung Ahn, Hyung Sik Lee, Se Kyung Bai, Chang Won Song
Radiation Oncology Journal.2013; 31(2): 57. CrossRef

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A Preliminary Results of a Randomized Trial Comparing Monthly 5-flourouracil and Cisplatin to Weekly Cisplatin Alone Combined with Concurrent Radiotherapy for Locally Advanced Cervical Cancer: Young Seok Kim, Seong Soo Shin, Eun Kyung Choi, Jong Hoon Kim, Seung Do Ahn, Sang-wook Lee, Heon-Jin Park, Young-Tak Kim, Jung-Eun Mok, Joo-Hyun Nam; Cancer Res Treat. 2005;37(1):37-43. Published online February 28, 2005; DOI: https://doi.org/10.4143/crt.2005.37.1.37

Abstract PDF PubReader ePub

Purpose

To determine the superior chemotherapeutic regimen between monthly 5-FU plus cisplatin (FP) and weekly cisplatin alone in concurrent chemoradiotherapy for locally advanced cervical cancer, the compliance of treatment, response, survival and toxicities were analyzed between the two arms.

Materials and Methods

Between March 1998 and December 2001, 61 patients with locally advanced cervical cancer (stage IIB through IVA) and negative para-aortic lymph nodes were randomly assigned to either 'monthly FP' (arm I, n=34) or 'weekly cisplatin' (arm II, n=27) with concurrent radiotherapy. The patients of arm I received FP (5-FU 1,000 mg/m²/day + cisplatin 20 mg/m²/day, for 5 days, for 3 cycles at 4 week intervals) and those of arm II received cisplatin (30 mg/m²/day, for 6 cycles at 1 week intervals) with concurrent radiotherapy. The radiotherapy consisted of 41.4~50.4 Gy external beam irradiation in 23~28 fractions to the whole pelvis, with high dose rate brachytherapy delivering a dose of 30~35 Gy in 6~7 fractions to point A. During the brachytherapy, a parametrial boost was delivered. The median follow-up period for survivors was 44 months.

Results

The compliance of treatment in monthly FP weekly cisplatin arms were 62 and 81%, respectively. The complete response rates at 3 months were 96 and 88% in arms I and II, respectively. The 4-year overall survival and disease free survival rates were 64 and 54% in the arm I and 77 and 66% in the arm II, respectively. The incidence of hematologic toxicity more than grade 2 was 29% in the arm I and 15% in the arm II. Only one patient in arm I experienced grade 3 gastrointestinal toxicity. No severe genitourinary toxicity was observed.

Conclusion

No significant difference was observed in the compliance, responses, survival rates and acute toxicities between the two treatment arms. More patients and further follow up will be required.

Citations

Citations to this article as recorded by

American Brachytherapy Task Group Report: A pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer
Jyoti Mayadev, Akila Viswanathan, Yu Liu, Chin-Shang Li, Kevin Albuquerque, Antonio L. Damato, Sushil Beriwal, Beth Erickson
Brachytherapy.2017; 16(1): 22. CrossRef
Concurrent Weekly Cisplatin Versus Triweekly Cisplatin with Radiotherapy in the Treatment of Cervical Cancer: A Meta-analysis Result
Yan Hu, Zhi-Qiang Cai, Xiao-Yan Su
Asian Pacific Journal of Cancer Prevention.2012; 13(9): 4301. CrossRef
Laparoscopy-Assisted Intracavitary Radiotherapy Tandem Placement for Patients With Cervical Cancer
Myong Cheol Lim, Dae Chul Jung, Joo-Young Kim, Sang-Yoon Park
International Journal of Gynecological Cancer.2009; 19(6): 1125. CrossRef
Adoptive Transfer of Human Papillomavirus E7-specific CTL Enhances Tumor Chemoresponse Through the Perforin/Granzyme-mediated Pathway
Jeong-Im Sin, Jung-Min Kim, Sung Hwa Bae, In Hee Lee, Jong Sup Park, Hun Mo Ryoo
Molecular Therapy.2009; 17(5): 906. CrossRef

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