Table 2. Mitochondrial protein synthesis inhibitory antibiotics tested for cancer treatment.

The chemical structures were obtained from Wikipedia (https://en.wikipedia.org).

ANTIBIOTIC	MECHANISM OF ACTION	TREATED CELL TYPES	REFS
Erythromycins	Binds to the LSU-rRNA complex in bacteria and mitochondria, and interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex.	Breast cancer Neuroblastoma	[¹–⁴]
Chloramphenicol	Binds to the LSU-rRNA complex in bacteria and mitochondria, specifically binds to A2451 and A2452 residues in the 23S rRNA, and interferes with peptidyl transferase, preventing protein chain elongation.	Breast cancer	[³]
Tetracyclines (Doxycycline)	Binds to the SSU-rRNA complex in bacteria and mitochondria, and prevents the interaction of aminoacyl-tRNA with the A site of the ribosome. The binding is reversible in nature.	Mesothelioma Leukemia Renal & prostate carcinomas Nephroma Lymphoma^* Leukemia	[⁵–⁷]
Glycylcyclines (Tigecycline)	Mechanism of action like tetracyclines.	Breast cancer	[⁸–¹⁰]
Actinonin	A hydroxamate-containing compound and strong inhibitor of metalloenzymes, especially matrix metalloproteases (MMPs). The hydroxamate group of actinonin acts as the chelating group to bind the metal ion of the enzyme.	Leukemia Lymphoma	[¹¹–¹³]
Aflatoxin B₁	A strong genotoxic hepatocarcinogen that induces DNA adducts, leading to genetic changes in the target cells, which then cause DNA strand breakage, DNA base damage and oxidative, presumptively results in cancer.	Hepatocarcinoma	[¹⁴–¹⁶]

Denotes a Clinical trial of doxycycline monotherapy to ocular adnexal lymphoma patients.

References

C. van den Bogert, B.H. Dontje, A.M. Kroon, The antitumour effect of doxycycline on a T-cell leukaemia in the rat, Leukemia research 9(5) (1985) 617–23.

C. van den Bogert, B.H. Dontje, M. Holtrop, T.E. Melis, J.C. Romijn, J.W. van Dongen, A.M. Kroon, Arrest of the proliferation of renal and prostate carcinomas of human origin by inhibition of mitochondrial protein synthesis, Cancer research 46(7) (1986) 3283–9.

R. Lamb, B. Ozsvari, C.L. Lisanti, H.B. Tanowitz, A. Howell, U.E. Martinez-Outschoorn, F. Sotgia, M.P. Lisanti, Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease, Oncotarget 6(7) (2015) 4569–84.

⁴

J. Yongsheng, M. Xiaoyun, W. Xiaoli, L. Xin, Y. Haitao, L. Xiaoyan, Z. Jianquan, Antitumor activity of erythromycin on human neuroblastoma cell line (SH-SY5Y), Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 31(1) (2011) 33–8.

⁵

A.J. Ferreri, S. Govi, E. Pasini, S. Mappa, F. Bertoni, F. Zaja, C. Montalban, C. Stelitano, M.E. Cabrera, A. Giordano Resti, L.S. Politi, C. Doglioni, F. Cavalli, E. Zucca, M. Ponzoni, R. Dolcetti, Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial, Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30(24) (2012) 2988–94.

⁶

⁷

C. van den Bogert, B.H. Dontje, A.M. Kroon, The antitumour effect of doxycycline on a T-cell leukaemia in the rat, Leuk. Res. 9(5) (1985) 617–23.

⁸

B. Jhas, S. Sriskanthadevan, M. Skrtic, M.A. Sukhai, V. Voisin, Y. Jitkova, M. Gronda, R. Hurren, R.C. Laister, G.D. Bader, M.D. Minden, A.D. Schimmer, Metabolic adaptation to chronic inhibition of mitochondrial protein synthesis in acute myeloid leukemia cells, PLoS One 8(3) (2013) e58367.

⁹

M. Skrtic, S. Sriskanthadevan, B. Jhas, M. Gebbia, X. Wang, Z. Wang, R. Hurren, Y. Jitkova, M. Gronda, N. Maclean, C.K. Lai, Y. Eberhard, J. Bartoszko, P. Spagnuolo, A.C. Rutledge, A. Datti, T. Ketela, J. Moffat, B.H. Robinson, J.H. Cameron, J. Wrana, C.J. Eaves, M.D. Minden, J.C. Wang, J.E. Dick, K. Humphries, C. Nislow, G. Giaever, A.D. Schimmer, Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia, Cancer cell 20(5) (2011) 674–88.

¹⁰

G.A. Reed, G.J. Schiller, S. Kambhampati, M.S. Tallman, D. Douer, M.D. Minden, K.W. Yee, V. Gupta, J. Brandwein, Y. Jitkova, M. Gronda, R. Hurren, A. Shamas-Din, A.C. Schuh, A.D. Schimmer, A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia, Cancer Med. 5(11) (2016) 3031–3040.

¹¹

D.Z. Chen, D.V. Patel, C.J. Hackbarth, W. Wang, G. Dreyer, D.C. Young, P.S. Margolis, C. Wu, Z.J. Ni, J. Trias, R.J. White, Z. Yuan, Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor, Biochemistry 39(6) (2000) 1256–62.

¹²

B. Peng, X. Zhang, F. Cao, Y. Wang, L. Xu, L. Cao, C. Yang, M. Li, G. Uzan, D. Zhang, Peptide deformylase inhibitor actinonin reduces celastrol’s HSP70 induction while synergizing proliferation inhibition in tumor cells, BMC Cancer 14 (2014) 146.

¹³

A. Sheth, S. Escobar-Alvarez, J. Gardner, L. Ran, M.L. Heaney, D.A. Scheinberg, Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc-overexpressing hematopoietic cancers, Cell death & disease 5 (2014) e1152.

¹⁴

A.S. Hamid, I.G. Tesfamariam, Y. Zhang, Z.G. Zhang, Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention, Oncology letters 5(4) (2013) 1087–1092.

¹⁵

X. Peng, K. Chen, J. Chen, J. Fang, H. Cui, Z. Zuo, J. Deng, Z. Chen, Y. Geng, W. Lai, Aflatoxin B1 affects apoptosis and expression of Bax, Bcl-2, and Caspase-3 in thymus and bursa of fabricius in broiler chickens, Environmental toxicology 31(9) (2016) 1113–20.

¹⁶

N.K. Bhat, J.K. Emeh, B.G. Niranjan, N.G. Avadhani, Inhibition of mitochondrial protein synthesis during early stages of aflatoxin B1-induced hepatocarcinogenesis, Cancer research 42(5) (1982) 1876–80.